Late metastasis of rectal adenocarcinoma to the penis.

Rectal cancer metastasising to the penis is an exceptionally rare clinical entity, with less than 80 reported cases. Metastasis to the penis is typically identified in conjunction with widespread metastatic disease and as such is usually associated with a very poor prognosis. We report a case of a man who presented with a metastatic deposit in his penis 15 years after the initial diagnosis of rectal cancer.

Interactive effect of dietary metabolizable energy levels with amino acid density in male broiler chickens: Carcass yield, nutrient intake, digestibility and excretion.

This study aimed to assess the interactive effects of ME and digestible amino acid (AA) densities on carcass yield, breast meat quality, nutrient digestibility, and excretion in male broiler chickens. Twelve experimental diets arranged as a 4 × 3 factorial array with 4 levels of ME (standard, -50, -100, -150 kcal) and 3 digestible AA (standard, +3.0 and +6.

Erroneous and Incomplete Reporting of the Pelvic Organ Prolapse Quantification System.

Introduction And Hypothesis: Accurate and complete reporting of the Pelvic Organ Prolapse Quantification (POP-Q) system is essential for reporting research outcomes in POP. We aimed to assess the accuracy and completeness of POP-Q reporting in studies published from selected journals in 2023 and evaluate the validity of available POP-Q calculators.

Methods: A systematic search of Medline and Embase was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify eligible studies from selected journals in 2023 that utilised the POP-Q system.

Comparative neurofilament light chain trajectories in CSF and plasma in autosomal dominant Alzheimer's disease.

Disease-modifying therapies for Alzheimer's disease (AD) are likely to be most beneficial when initiated in the presymptomatic phase. To track the benefit of such interventions, fluid biomarkers are of great importance, with neurofilament light chain protein (NfL) showing promise for monitoring neurodegeneration and predicting cognitive outcomes. Here, we update and complement previous findings from the Dominantly Inherited Alzheimer Network Observational Study by using matched cross-sectional and longitudinal cerebrospinal fluid (CSF) and plasma samples from 567 individuals, allowing timely comparative analyses of CSF and blood trajectories across the entire disease spectrum.

Zerlasiran-A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial.

Importance: Elevated lipoprotein(a) increases the risk of atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis.

Objective: To evaluate the effects of zerlasiran, a small-interfering RNA targeting hepatic synthesis of apolipoprotein(a), on lipoprotein(a) serum concentration.

Design, Setting, And Participants: A multicenter trial in patients with stable ASCVD with serum lipoprotein(a) concentrations greater than or equal to 125 nmol/L at 26 sites in Europe and South Africa between January 3, 2023, and April 27, 2023, with last follow-up on July 1, 2024.

Easy-MODA: Simplifying standardised registration of scientific simulation workflows through MODA template guidelines powered by the Enalos Cloud Platform.

Modelling Data (MODA) reporting guidelines have been proposed for common terminology and for recording metadata for physics-based materials modelling and simulations in a CEN Workshop Agreement (CWA 17284:2018). Their purpose is similar to that of the Quantitative Structure-Activity Relationship (QSAR) model report form (QMRF) that aims to increase industry and regulatory confidence in QSAR models, but for a wider range of model types. Recently, the WorldFAIR project's nanomaterials case study suggested that both QMRF and MODA templates are an important means to enhance compliance of nanoinformatics models, and their underpinning datasets, with the FAIR principles (Findable, Accessible, Interoperable, Reusable).

4-(Pyrazolyl)benzenesulfonamide Ureas as Carbonic Anhydrases Inhibitors and Hypoxia-Mediated Chemo-Sensitizing Agents in Colorectal Cancer Cells.

Hypoxia in tumors contributes to chemotherapy resistance, worsened by acidosis driven by carbonic anhydrases (CA IX and XII). Targeting these enzymes can mitigate acidosis, thus enhancing tumor sensitivity to cytotoxic drugs. Herein, novel 4-(pyrazolyl)benzenesulfonamide ureas () were developed and evaluated for their inhibitory activity against CA IX and XII.

Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial.

Background: Glofitamab monotherapy induces durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma after two or more previous therapies, but has not previously been assessed as a second-line therapy. We investigated the efficacy and safety of glofitamab plus gemcitabine-oxaliplatin (Glofit-GemOx) versus rituximab (R)-GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma.

Methods: The phase 3, randomised, open-label STARGLO trial was done at 62 centres in 13 countries in Asia and Australia, Europe, and North America.

A comprehensive review of the proline mimic azetidine-2-carboxylic acid (A2C).

The imino acid azetidine-2-carboxylic acid (A2C), a proline homologue, was first identified in liliaceous plants in 1955. Its ability to exchange for proline in protein synthesis is responsible for its teratogenic effects and has made it a very useful tool for generating non-native proteins to study proteotoxic stress and ER stress. The tRNA synthetases from some A2C-producing plants can discriminate between proline and A2C, but for most plants and for mammalian cells, A2C is mistakenly used in protein synthesis in place of proline and can avoid cell proof-reading mechanisms.

Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial.

Background: Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, has been shown to reduce hunger and weight in patients aged 6 years and older with proopiomelanocortin (POMC) deficiency (including biallelic variants in proprotein convertase subtilisin/kexin type 1 [PCSK1]), leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS). No approved therapies for patients younger than 6 years old currently exist. The phase 3, open-label VENTURE trial aimed to evaluate the efficacy and safety of setmelanotide in patients aged 2-5 years with POMC or LEPR deficiency or BBS.

Evaluation of Myocarditis in Patients With Still Disease: Clinical Findings From the Multicenter International AIDA Network Still Disease Registry.

Objective: We aimed to (1) evaluate the cardiac involvement, with a focus on myocarditis, in patients with Still disease included in the multicenter Autoinflammatory Disease Alliance (AIDA) Network Still disease registry; and (2) assess the predictive factors for myocarditis by deriving a clinical risk patient profile for this severe manifestation.

Methods: A multicenter observational study was established, in which consecutive patients with Still disease in the AIDA Network Still disease registry were characterized by cardiac involvement. Cardiac involvement was defined according to the presence of pericarditis, tamponade, myocarditis, and/or aseptic endocarditis.

Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis.

Background: In Europe, approximately 291,000 cardiac arrests occur annually. Despite critical care therapy, hospital mortality remains high. This systematic review assessed whether, in comatose survivors of cardiac arrest, any drug therapy, compared to placebo or usual care, improves outcomes.

Association of alcohol with lung cancer risk in men with different growth hormone receptor genotypes.

Objective: To test whether genetic variants of the growth hormone receptor gene (GHR) modulate the effect of lifestyle variables on lung cancer (LC) risk.

Materials And Methods: This population-based cohort study involved 6,439 men from the Japan-Hawaii Cancer study drawn from the Kuakini Honolulu Heart Program who were cancer-free at baseline examination (1965-1968; age 45-68 years) and followed-up until December 1999. We determined the association of GHR SNP rs4130113 genotypes GHR-AA (common allele A homozygotes) and GHR-G (minor allele G carriage) with alcohol drinking, BMI, physical activity and cigarette smoking in relation to LC and non-small cell LC (NSCLC).

The Utilization of the Accelerated Approval Pathway in Oncology: A Case Study of Pembrolizumab.

The accelerated approval (AA) pathway was established by the United States Food and Drug Administration (FDA) to provide earlier access to therapies for patients with serious medical conditions and unmet medical needs. Since its inception, the AA pathway has been used for novel treatments across different therapeutic areas, but most prominently in oncology, including the immune checkpoint inhibitor class. This review article describes the history of regulatory approvals for pembrolizumab, an immunotherapy agent targeting programmed death receptor-1 (PD-1), and use of the AA pathway and the corresponding regulatory decisions made by the FDA.

Gaps in biomedical research in frontotemporal dementia: A call for diversity and disparities focused research.

Frontotemporal dementia (FTD) is one of the leading causes of young-onset dementia before age 65, typically manifesting as abnormal behavior (in behavioral variant FTD) or language impairment (in primary progressive aphasia). Although FTD affects all populations across the globe, knowledge regarding the pathophysiology and genetics derives primarily from studies conducted in North America and Western Europe. Globally, biomedical research for FTD is hindered by variable access to diagnosis, discussed in this group's earlier article, and by reduced access to expertise, funding, and infrastructure.

Pembrolizumab 400 mg every 6 weeks as first-line therapy for advanced melanoma (KEYNOTE-555): Results from cohort B of an open-label, phase 1 study.

Intravenous pembrolizumab 400 mg every 6 weeks was approved across tumor types based on pharmacokinetic modeling, which showed exposures consistent with previous standard dosing of 200 mg or 2 mg/kg every 3 weeks, and early results of cohort B of the phase 1 KEYNOTE-555 study. Results after ≥1 year of potential follow-up for all patients in cohort B of KEYNOTE-555 are presented. Patients aged ≥18 years with previously untreated stage III/IV melanoma received pembrolizumab 400 mg every 6 weeks for ≤18 cycles.